Experimental evidence and ecologic correlation studies support the hypothesis that vitamin D may reduce breast cancer risk. Yet this novel hypothesis is largely untested in human populations. An on-going population-based case-control study of breast cancer in Hispanic, African-American, and White Women will assess the associations with sunlight exposure and dietary vitamin D intake. On-going molecular research by one of the investigations of this applications suggests that polymorphisms of the vitamin D receptor (VDR) gene are related to the breast cancer risk. We therefore propose to expand the on-going case- control study in order to broaden our examination of the relation with vitamin D. In addition to the interview data being collected, we propose to obtain blood samples for a subset of study participants and to extend the case and control ascertainment by 10 months. Eligible cases will include women aged 35-79 and diagnosed with invasive breast cancer between May 1997 and February 1999. Cases will be identified through the cancer registries in the Greater San Francisco Bay area; controls will be selected from the general population through random-digit dialing. Professional interviewers will collect interview data, measure skin pigmentation, and obtain blood specimens through home visits. Blood specimens and risk factor data will be available for an estimated 640 cases (245 Hispanics, 225 Whites, and 170 African-Americans) and 960 controls (365 Hispanics, 340 Whites, and 255 African-Americans). We will assess (1) the association with two markers (poly-A and FOKI) of the VDR gene in Hispanics and Whites; (2) the association with the BsmI/poly-A haplotype in African-Americans; and (3) the possible modifying effect of VDR genotype on the association with sunlight exposure and dietary vitamin D intake. We will also bank DNA, buffy coat, and plasma for future molecular epidemiologic studies. Building upon the infrastructure of the on-going study, we have the opportunity to establish a valuable resource for more thoroughly assessing the relationship between vitamin D and breast cancer risk; for conducting future molecular epidemiologic research as new biomarkers and genes will be identified in the future; and for investigating gene-environment interactions in a multi-ethnic population. Since vitamin D exposure is potentially modifiable, the proposed research may have important implications for new approaches to breast cancer prevention.